PB2085: UPFRONT TREATMENT OF MANTLE CELL LYMPHOMA (MCL) WITH R-HDAC (RITUXIMAB-HIGH DOSE CYTARABINE + DEXAMETHASONE) IN YOUNG, HIGH RISK PATIENTS IS WELL TOLERATED AND LEADS TO DURABLE RESPONSES.
Authors: G. U. Naylor, S. Mant, C. Bedford, D. Turner, M. Furtado, D. Lewis
Journal: HemaSphere (2022)

Background: MCL commonly presents as aggressive disease with a low cure rate and multiply relapsing/remitting course. Treatment of classical MCL with upfront intensive chemoimmunotherapy (CIT) consolidated with an autologous stem cell transplant (ASCT) is considered best practice in younger patients. There is no gold standard intensive CIT regimen. Common approaches include alternating RCHOP/RDHAP (Nordic) and R-Hyper-CVAD.(1) The addition of high dose Cytarabine (HDAC) has been shown to improve time to treatment failure (TTF), complete response (CR) rates and progression free survival (PFS). Aims: There is little published on the efficacy of R-HDAC in treatment-naive MCL, however a 2013 case series (Forbes et al) reported good early efficacy (CR in 16/18), with no detriment to harvest success. We describe tolerability and efficacy of upfront R-HDAC in a high risk cohort of younger patients with MCL. Methods: We identified 28 patients who received upfront R-HDAC in 3 UK centres from 2010–2021. Data were collected, anonymized and transferred centrally for analysis using Kaplan-Meier survival curves. Results: For baseline characteristics see Table 1. Treatment regimen: Dexamethasone 40mg d1-d4, Rituximab 500mg d1, Cytarabine 3000mg/m2 BD d2-d3 in 21day cycles. 22/28 (79%) completed their planned quota of 4-6cycles; 6/28 (21%) did not. Of these n=5 had progressive disease (PD), n=1 ceased with toxicity. 4/28 incurred cycle delays. 1 patient developed PD after completing R-HDAC. Haematological toxicity ≥ Grade 3 CTCAE: Anaemia 71%; Thrombocytopenia 93%; Neutropenia 93%. Fatigue (57%), Nausea 25%, Vomiting 7%, Constipation 21%, Diarrhoea 11%, Cardiac toxicity 11%, Pulmonary toxicity 18%, Rash 11%. 20/28 (71%) underwent stem cell transplant consolidation of which 19 had an ASCT. The median CD34+ stem cell harvest was 8.3x109^L/Kg (2.56-40.9) with no harvest failures. One patient underwent an allogeneic SCT. Of those who didn’t undergo transplant: 1/8 declined; 1/8 was ineligible; 6/8 had PD and switched to 2nd line therapy. Overall Response Rate (ORR) (RECIST) was 78%, CR 41%; PR (Partial response) 37%; and PD 22%. The median PFS was 3.39years (95% CI 0-7.937). 5y OS was 64.3% (95% CI 44.9-83.7%), median OS 8.7years (95% CI 2.634 – 14.894). Image:Summary/Conclusion: Our cohort showed higher rates of haematological toxicity, but lower gastrointestinal toxicity than those reported with the Nordic approach.(1) There were no incidents of treatment related mortality (TRM). More intensive regimens e.g. R-Hyper-CVAD have documented TRM rates of up to 8%. Only 1 patient in our cohort ceased treatment because of toxicity. Whilst our ORR is lower than those published in trial data on commonly used regimens (78% vs MCL Younger trial ORR: RCHOP arm 90%/Cytarabine arm 94%) our cohort’s baseline demographics are comparably much higher risk: MIPIb High 53% vs 25/20%; Blastoid disease 25% vs 9/8%. Of those with PD in our cohort, 4/6 had high MIPIb and blastoid disease. Despite this disparity, R-HDAC retains a comparable CR rate (41% vs 38%) and 5y OS (64.3% vs 65%). Whilst this observational retrospective study has limitations, it has shown that R-HDAC is an option for younger patients with high risk MCL. Using fewer CIT drugs could reduce toxicity and reserve more agents for use in future relapse. References: 1. Hermine, O. et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016;388(10044):565-75.